Understanding experience-dependent plasticity of cellular and network activity in the mouse primary visual cortex

Abstract

Sensory experiences in daily life modulates corresponding primary sensory cortices and eventually alter our behavior in a befitting manner. One of the most impactful sensory modules is vision. Primary visual cortex (V1) in mammals is particularly malleable during a juvenile critical period, but this plasticity lasts even in adulthood. A representative form of visual cortical plasticity is ocular dominance (OD) plasticity following temporary monocular deprivation (MD). Here, we used a mouse model of amblyopia and revealed that juvenile OD plasticity, which manifests as depression of response to the deprived eye, requires expression of an immediate early gene, Arc. Also, the juvenile OD shift requires the activity of N-methyl-D-aspartate (NMDA) receptors in layer 4 excitatory principal neurons in V1. Another simple but powerful phenomenon of an adult form of visual cortical plasticity is stimulus-selective response potentiation (SRP). SRP is induced simply through experience to the same gratings visual stimulus over days, resulting in potentiation of visually-evoked potentials (VEPs) in layer 4 of V1. Due to the lack of studies regarding the cellular and network activity changes coincident with the induction of SRP, we have used calcium indicator expressing mice to visualize cellular activity across days of SRP training. Using two-photon calcium imaging, we found that there is indeed no significant net change in the population of active neurons during presentation of the familiar (trained) visual stimulus. Follow-up endoscopic calcium imaging revealed that rather, there is a significant reduction of somatic calcium responses selectively for the familiar visual stimulus on the test day following 5 days of SRP induction. Interestingly, the cellular calcium response to the first presentation of the familiar visual stimulus in each block was substantially similar to the response to those of a novel, yet unseen visual stimulus. However, calcium responses to the familiar visual stimulus dramatically decreased as stimulation was repeated in each presentation block within, and across days of SRP training, whereas the response to the novel visual stimulus on the test day was maintained. The findings that short-latency VEP responses are potentiated, while the slower responses revealed by calcium imaging are depressed suggest that feedback inhibition in V1 is strongly recruited by visual recognition of familiar stimulus. A number of previous studies have suggested that deficits in experience-dependent sensory cortical plasticity and perceptual learning are associated with neuropsychiatric disorders such as autism spectrum disorder (ASD), Rett syndrome and schizophrenia. Our results, therefore, may contribute to our understanding of the underlying mechanisms of these disorders and may help inform ways of intervention and treatments.